A Dose-ranging Study of Orvepitant in Patients With Chronic Refractory Cough
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| ClinicalTrials.gov Identifier: NCT02993822 |
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Recruitment Status :
Completed
First Posted : December 15, 2016
Results First Posted : April 26, 2022
Last Update Posted : April 26, 2022
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Sponsor:
Nerre Therapeutics Ltd.
Information provided by (Responsible Party):
Nerre Therapeutics Ltd.
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Brief Summary:
The purpose of this study is to determine the effectiveness of three doses of orvepitant, taken once a day, in the treatment of chronic refractory cough.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Chronic Refractory Cough | Drug: Orvepitant Maleate Drug: Placebo | Phase 2 |
A multi-center, double-blind, randomized, parallel group, placebo-controlled dose range study in subjects with chronic refractory cough (CRC).
Doses of orvepitant (10 mg/day, 20 mg/day and 30 mg/day) and placebo will be investigated in four parallel groups.
Each group will compromise of approximately 73 subjects, randomized 1:1:1:1 (approximately 292 subjects in total).
All subjects will enter a three-week screening period to determine eligibility. Eligible subjects will be randomized at the Baseline/Day 1 visit and enter a 12-week double-blind dosing period. During this period there will be four visits at Weeks 2, 4, 8 and 12. There will be a final safety follow-up visit at Week 14.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 315 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | A Double-Blind, Randomized, Placebo Controlled Study of the Efficacy and Safety of Three Doses of Orvepitant in Subjects With Chronic Refractory Cough |
| Actual Study Start Date : | May 22, 2017 |
| Actual Primary Completion Date : | January 14, 2019 |
| Actual Study Completion Date : | January 24, 2019 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Orvepitant 10mg
Orvepitant 10mg tablet, once daily for 12 weeks
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Drug: Orvepitant Maleate
Tablet, once daily, oral |
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Experimental: Orvepitant 20mg
Orvepitant 20mg tablet, once daily for 12 weeks
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Drug: Orvepitant Maleate
Tablet, once daily, oral |
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Experimental: Orvepitant 30mg
Orvepitant 30mg tablet, once daily for 12 weeks
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Drug: Orvepitant Maleate
Tablet, once daily, oral |
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Placebo Comparator: Placebo
Placebo to match tablet, once daily for 12 weeks
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Drug: Placebo
Tablet, once daily, oral |
Primary Outcome Measures :
- Change From Baseline to Week 12 in Awake Objective Cough Frequency [ Time Frame: Baseline to Week 12 ]Objective cough frequency measured by ambulatory cough monitoring device
Secondary Outcome Measures :
- Change in Awake Objective Cough Frequency at Week 2 Compared to Baseline [ Time Frame: Baseline to Week 2 ]Objective cough frequency measured by ambulatory cough monitoring device
- Change in Awake Objective Cough Frequency at Week 4 Compared to Baseline [ Time Frame: Week 4 ]Objective cough frequency measured by ambulatory cough monitoring device
- Change in the Leicester Cough Questionnaire (LCQ) at Week 2 Compared to Baseline [ Time Frame: Baseline to Week 2 ]The Leicester Cough Questionnaire (LCQ) is a 19 item questionnaire that assessed cough related quality of life. It has three domains (physical, psychological and social) and subjects were asked to complete it based on their experience in a recall period of 2 weeks. The total score range is 3 to 21 and domain scores each range from 1 to 7; a higher score indicated a better quality of life. Subjects completed the LCQ whilst in the clinic at baseline/Day 1 (pre dose) and at Weeks 2, 4, 8, and 12.
- Change in the Leicester Cough Questionnaire (LCQ) at Week 4 Compared to Baseline [ Time Frame: Baseline to Week 4 ]The Leicester Cough Questionnaire (LCQ) is a 19 item questionnaire that assessed cough related quality of life. It has three domains (physical, psychological and social) and subjects were asked to complete it based on their experience in a recall period of 4 weeks. The total score range is 3 to 21 and domain scores each range from 1 to 7; a higher score indicated a better quality of life. Subjects completed the LCQ whilst in the clinic at baseline/Day 1 (pre dose) and at Weeks 2, 4, 8, and 12.
- Change in the Leicester Cough Questionnaire (LCQ) at Week 8 Compared to Baseline [ Time Frame: Baseline to Week 8 ]The Leicester Cough Questionnaire (LCQ) is a 19 item questionnaire that assessed cough related quality of life. It has three domains (physical, psychological and social) and subjects were asked to complete it based on their experience in a recall period of 8 weeks. The total score range is 3 to 21 and domain scores each range from 1 to 7; a higher score indicated a better quality of life. Subjects completed the LCQ whilst in the clinic at baseline/Day 1 (pre dose) and at Weeks 2, 4, 8, and 12.
- Change in the Leicester Cough Questionnaire (LCQ) at Week 12 Compared to Baseline [ Time Frame: Baseline to Week 12 ]The Leicester Cough Questionnaire (LCQ) is a 19 item questionnaire that assessed cough related quality of life. It has three domains (physical, psychological and social) and subjects were asked to complete it based on their experience in a recall period of 12 weeks. The total score range is 3 to 21 and domain scores each range from 1 to 7; a higher score indicated a better quality of life. Subjects completed the LCQ whilst in the clinic at baseline/Day 1 (pre dose) and at Weeks 2, 4, 8, and 12.
- Change in the Cough Severity Visual Analogue Scale (VAS) at Week 2 Compared to Baseline - Day-time [ Time Frame: Baseline to Week 2 ]The cough VAS is a 100 mm scale on which subjects indicated their severity of cough over the previous 24 hours, both during the day-time and during night time separately. The VAS ranged from "no cough" (0 mm) on the left to "worst cough" (100 mm) on the right. Subjects completed the cough severity VAS at baseline/Day 1 (pre dose) and at Weeks 2, 4, 8, and 12.
- Change in the Cough Severity Visual Analogue Scale (VAS) at Week 4 Compared to Baseline - Day-time [ Time Frame: Baseline to Week 4 ]The cough VAS is a 100 mm scale on which subjects indicated their severity of cough over the previous 24 hours, both during the day-time and during night time separately. The VAS ranged from "no cough" (0 mm) on the left to "worst cough" (100 mm) on the right. Subjects completed the cough severity VAS at baseline/Day 1 (pre dose) and at Weeks 2, 4, 8, and 12.
- Change in the Cough Severity Visual Analogue Scale (VAS) at Week 8 Compared to Baseline - Day-time [ Time Frame: Baseline to Week 8 ]The cough VAS is a 100 mm scale on which subjects indicated their severity of cough over the previous 24 hours, both during the day-time and during night time separately. The VAS ranged from "no cough" (0 mm) on the left to "worst cough" (100 mm) on the right. Subjects completed the cough severity VAS at baseline/Day 1 (pre dose) and at Weeks 2, 4, 8, and 12.
- Change in the Cough Severity Visual Analogue Scale (VAS) at Week 12 Compared to Baseline - Day-time [ Time Frame: Baseline to Week 12 ]The cough VAS is a 100 mm scale on which subjects indicated their severity of cough over the previous 24 hours, both during the day-time and during night time separately. The VAS ranged from "no cough" (0 mm) on the left to "worst cough" (100 mm) on the right. Subjects completed the cough severity VAS at baseline/Day 1 (pre dose) and at Weeks 2, 4, 8, and 12.
- Change in the Cough Severity Visual Analogue Scale (VAS) at Week 2 Compared to Baseline - Night-time [ Time Frame: Baseline to Week 2 ]The cough VAS is a 100 mm scale on which subjects indicated their severity of cough over the previous 24 hours, both during the day-time and during night time separately. The VAS ranged from "no cough" (0 mm) on the left to "worst cough" (100 mm) on the right. Subjects completed the cough severity VAS at baseline/Day 1 (pre dose) and at Weeks 2, 4, 8, and 12.
- Change in the Cough Severity Visual Analogue Scale (VAS) at Week 4 Compared to Baseline - Night-time [ Time Frame: Baseline to Week 4 ]The cough VAS is a 100 mm scale on which subjects indicated their severity of cough over the previous 24 hours, both during the day-time and during night time separately. The VAS ranged from "no cough" (0 mm) on the left to "worst cough" (100 mm) on the right. Subjects completed the cough severity VAS at baseline/Day 1 (pre dose) and at Weeks 2, 4, 8, and 12.
- Change in the Cough Severity Visual Analogue Scale (VAS) at Week 8 Compared to Baseline - Night-time [ Time Frame: Baseline to Week 8 ]The cough VAS is a 100 mm scale on which subjects indicated their severity of cough over the previous 24 hours, both during the day-time and during night time separately. The VAS ranged from "no cough" (0 mm) on the left to "worst cough" (100 mm) on the right. Subjects completed the cough severity VAS at baseline/Day 1 (pre dose) and at Weeks 2, 4, 8, and 12.
- Change in the Cough Severity Visual Analogue Scale (VAS) at Week 12 Compared to Baseline - Night-time [ Time Frame: Baseline to Week 12 ]The cough VAS is a 100 mm scale on which subjects indicated their severity of cough over the previous 24 hours, both during the day-time and during night time separately. The VAS ranged from "no cough" (0 mm) on the left to "worst cough" (100 mm) on the right. Subjects completed the cough severity VAS at baseline/Day 1 (pre dose) and at Weeks 2, 4, 8, and 12.
- Change in the Urge-to-cough Visual Analogue Scale (VAS) at Week 2 Compared to Baseline [ Time Frame: Baseline to Week 2 ]The urge-to-cough VAS was a 100 mm scale on which subjects indicated their urge to cough over the previous 24 hours (day/awake time and night time combined). The VAS ranged from "no urge to cough" (0 mm) on the left to "severe urge to cough" (100 mm) on the right. Subjects completed the urge to cough VAS at baseline/Day 1 (pre dose) and at Weeks 2, 4, 8, and 12.
- Change in the Urge-to-cough Visual Analogue Scale (VAS) at Week 4 Compared to Baseline [ Time Frame: Baseline to Week 4 ]The urge-to-cough VAS was a 100 mm scale on which subjects indicated their urge to cough over the previous 24 hours (day/awake time and night time combined). The VAS ranged from "no urge to cough" (0 mm) on the left to "severe urge to cough" (100 mm) on the right. Subjects completed the urge to cough VAS at baseline/Day 1 (pre dose) and at Weeks 2, 4, 8, and 12.
- Change in the Urge-to-cough Visual Analogue Scale (VAS) at Week 8 Compared to Baseline [ Time Frame: Baseline to Week 8 ]The urge-to-cough VAS was a 100 mm scale on which subjects indicated their urge to cough over the previous 24 hours (day/awake time and night time combined). The VAS ranged from "no urge to cough" (0 mm) on the left to "severe urge to cough" (100 mm) on the right. Subjects completed the urge to cough VAS at baseline/Day 1 (pre dose) and at Weeks 2, 4, 8, and 12.
- Change in the Urge-to-cough Visual Analogue Scale (VAS) at Week 12 Compared to Baseline [ Time Frame: Baseline to Week 12 ]The urge-to-cough VAS was a 100 mm scale on which subjects indicated their urge to cough over the previous 24 hours (day/awake time and night time combined). The VAS ranged from "no urge to cough" (0 mm) on the left to "severe urge to cough" (100 mm) on the right. Subjects completed the urge to cough VAS at baseline/Day 1 (pre dose) and at Weeks 2, 4, 8, and 12.
- Global Rating of Change in Cough Frequency at Week 2 [ Time Frame: Baseline to Week 2 ]In the Global Rating of Change scale, subjects indicated if there had been a change in their symptoms (cough frequency and, separately, cough severity) since starting the IMP. Subjects responded with "worse", "about the same" or "better". If subjects indicated a change (either "worse" or "better") they then indicated on a 7 point scale the degree of change ranging from 1 (almost the same, hardly any change) to 7 (a very great deal changed). Subjects documented their Global Rating of Change in cough frequency and cough severity at Weeks 2, 4, 8, and 12.
- Global Rating of Change in Cough Frequency at Week 4 [ Time Frame: Baseline to Week 4 ]In the Global Rating of Change scale, subjects indicated if there had been a change in their symptoms (cough frequency and, separately, cough severity) since starting the IMP. Subjects responded with "worse", "about the same" or "better". If subjects indicated a change (either "worse" or "better") they then indicated on a 7 point scale the degree of change ranging from 1 (almost the same, hardly any change) to 7 (a very great deal changed). Subjects documented their Global Rating of Change in cough frequency and cough severity at Weeks 2, 4, 8, and 12.
- Global Rating of Change in Cough Frequency at Week 8 [ Time Frame: Baseline to Week 8 ]In the Global Rating of Change scale, subjects indicated if there had been a change in their symptoms (cough frequency and, separately, cough severity) since starting the IMP. Subjects responded with "worse", "about the same" or "better". If subjects indicated a change (either "worse" or "better") they then indicated on a 7 point scale the degree of change ranging from 1 (almost the same, hardly any change) to 7 (a very great deal changed). Subjects documented their Global Rating of Change in cough frequency and cough severity at Weeks 2, 4, 8, and 12.
- Global Rating of Change in Cough Frequency at Week 12 [ Time Frame: Baseline to Week 12 ]In the Global Rating of Change scale, subjects indicated if there had been a change in their symptoms (cough frequency and, separately, cough severity) since starting the IMP. Subjects responded with "worse", "about the same" or "better". If subjects indicated a change (either "worse" or "better") they then indicated on a 7 point scale the degree of change ranging from 1 (almost the same, hardly any change) to 7 (a very great deal changed). Subjects documented their Global Rating of Change in cough frequency and cough severity at Weeks 2, 4, 8, and 12.
- Global Rating of Change in Cough Severity at Week 2 [ Time Frame: Baseline to Week 2 ]In the Global Rating of Change scale, subjects indicated if there had been a change in their symptoms (cough frequency and, separately, cough severity) since starting the IMP. Subjects responded with "worse", "about the same" or "better". If subjects indicated a change (either "worse" or "better") they then indicated on a 7 point scale the degree of change ranging from 1 (almost the same, hardly any change) to 7 (a very great deal changed). Subjects documented their Global Rating of Change in cough frequency and cough severity at Weeks 2, 4, 8, and 12.
- Global Rating of Change in Cough Severity at Week 4 [ Time Frame: Baseline to Week 4 ]In the Global Rating of Change scale, subjects indicated if there had been a change in their symptoms (cough frequency and, separately, cough severity) since starting the IMP. Subjects responded with "worse", "about the same" or "better". If subjects indicated a change (either "worse" or "better") they then indicated on a 7 point scale the degree of change ranging from 1 (almost the same, hardly any change) to 7 (a very great deal changed). Subjects documented their Global Rating of Change in cough frequency and cough severity at Weeks 2, 4, 8, and 12.
- Global Rating of Change in Cough Severity at Week 8 [ Time Frame: Baseline to Week 8 ]In the Global Rating of Change scale, subjects indicated if there had been a change in their symptoms (cough frequency and, separately, cough severity) since starting the IMP. Subjects responded with "worse", "about the same" or "better". If subjects indicated a change (either "worse" or "better") they then indicated on a 7 point scale the degree of change ranging from 1 (almost the same, hardly any change) to 7 (a very great deal changed). Subjects documented their Global Rating of Change in cough frequency and cough severity at Weeks 2, 4, 8, and 12.
- Global Rating of Change in Cough Severity at Week 12 [ Time Frame: Baseline to Week 12 ]In the Global Rating of Change scale, subjects indicated if there had been a change in their symptoms (cough frequency and, separately, cough severity) since starting the IMP. Subjects responded with "worse", "about the same" or "better". If subjects indicated a change (either "worse" or "better") they then indicated on a 7 point scale the degree of change ranging from 1 (almost the same, hardly any change) to 7 (a very great deal changed). Subjects documented their Global Rating of Change in cough frequency and cough severity at Weeks 2, 4, 8, and 12.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Key Inclusion Criteria:
- Male and female subjects ≥18 years of age.
- Diagnosis of CRC or unexplained cough for at least 1 year (see ACCP/BTS guidelines attached).
- An awake average cough frequency of ≥10 coughs/ hour, as assessed using an ACM during the screening period.
Key Exclusion Criteria:
- Subjects with respiratory tract infection (<4 weeks prior to study start)
- Current smokers or ex-smokers with <6 months' abstinence or cumulative history of >10 pack years
- Treatment with Angiotensin Converting Enzyme (ACE) inhibitors within 3 months of screening
- FEV1 <80% predicted, measured at screening using spirometry
- History of cystic fibrosis, idiopathic pulmonary fibrosis, clinically significant bronchiectasis, moderate to severe asthma, chronic obstructive pulmonary disease (COPD)
- Any clinically significant abnormal laboratory test result(s)
- Inability to comply with the use of prohibited and allowed medications as described in the protocol.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02993822
Locations
Show 66 study locations
Sponsors and Collaborators
Nerre Therapeutics Ltd.
Study Documents (Full-Text)
Documents provided by Nerre Therapeutics Ltd.:
Documents provided by Nerre Therapeutics Ltd.:
Study Protocol [PDF] February 21, 2018
Statistical Analysis Plan [PDF] May 8, 2018
| Responsible Party: | Nerre Therapeutics Ltd. |
| ClinicalTrials.gov Identifier: | NCT02993822 |
| Other Study ID Numbers: |
VOLCANO-2 |
| First Posted: | December 15, 2016 Key Record Dates |
| Results First Posted: | April 26, 2022 |
| Last Update Posted: | April 26, 2022 |
| Last Verified: | March 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Cough Respiration Disorders Respiratory Tract Diseases Signs and Symptoms, Respiratory |
Maleic acid Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |